PROJECT SUMMARY ABSTRACT FOR THE NVSN CORE The purpose of this project is to support a network of US pediatric institutions to conduct prospective, active surveillance in defined inpatient and emergency department (ED) populations for acute gastroenteritis (AGE) and acute respiratory illnesses (ARI) and in asymptomatic healthy controls for evaluation of disease burden and annual estimates of influenza and rotavirus vaccine effectiveness (VE). The results from this program will be used to inform vaccine recommendations and assess the public health impact of the US rotavirus and influenza vaccination programs and provide epidemiologic data for other infectious diseases with therapeutics and vaccines in development. A second purpose is to prospectively follow children from birth to age two for a natural history study of pathogens and immunologic factors related to symptomatic and asymptomatic infection. Our proposal for this study is provided separately as an Optional Component. The first objective is to evaluate the effectiveness and impact of current or upcoming vaccines or other immunoprophylaxis strategies and to inform pediatric vaccine-related policies. This will be done through the AGE and ARI active surveillance program. The rotavirus and influenza vaccine programs will be evaluated. Children with AGE enrolled in the hospital and ED will have stool tested for rotavirus and rotavirus vaccine verification completed. Using a test-negative design, the vaccination status of children with laboratory- confirmed rotavirus will be compared to children testing negative for rotavirus to determine the effectiveness of rotavirus vaccines by age and vaccine type. Children > 6 months to 18 years of age hospitalized for ARI will be enrolled, nasal and throat swabs will be tested by influenza RT-PCR and vaccine verification will be completed. VE estimates will be made using a test-negative study design by age, vaccine type and influenza sub-types. The secondary objective is to actively assess the burden of AGE and ARI pathogens in pediatric hospital and ED populations using sensitive laboratory techniques on specimens collected during the 5 years of the project. A separate healthy control surveillance program will provide age and season frequency matched children for comparison to ill children for both AGE and ARI pathogens. Age- and pathogen-specific population-based estimates of incidence will be made by site and setting (hospital and ED). A third objective is to examine the epidemiologic, host and environmental factors that are relevant for public health interventions of vaccine preventable diseases and diseases in need of preventive or treatment strategies. This will be done through investigator-initiated proposals through the surveillance and optional component. This surveillance network and its associated activities will lead to high impact public health findings in the field of vaccine preventable diseases that will ultimately contribute to strategies to reduce the overall healthcare burden from these diseases and improve the health of the US population.